Health care-associated Clostridioides difficile infection: Learning the perspectives of health care workers to build successful strategies.

BACKGROUND: Clostridioides difficile (C difficile) is one of the most common health care-associated infections that negatively impact patient care and health care costs. This study takes a unique approach to C difficile infection (CDI) control by investigating key prevention obstacles through the perspectives of Stanford health care (SHC) frontline health care personnel. METHODS: An anonymous qualitative survey was distributed at SHC, focusing on knowledge and practice of CDI prevention guidelines, as well as education, communication, and perspectives regarding CDI at SHC. RESULTS: 112 survey responses were analyzed. Our findings unveiled gaps in personnel's knowledge of C difficile diagnostic guidelines and revealed a need for targeted communication and guideline-focused education. Health care staff shared preferences and recommendations, with the majority recommending enhanced communication of guidelines and information as a strategy for reducing CDI rates. The findings were then used to design and propose internal recommendations for SHC to mitigate the gaps found. DISCUSSION: Many guidelines and improvement strategies are based on strong scientific and medical foundations; however, it is important to ask whether these guidelines are effectively translated into practice. Frontline health care workers hold empirical perspectives that could be key in infection control. CONCLUSIONS: Our findings emphasize the importance of including frontline health care personnel in infection prevention decision-making processes and the strategies presented here can be applied to mitigating infections in different health care settings.

Wake-up call for HPPP - health promotion, prevention, and preparedness.

The latest public health emergencies exposed urgent gaps in health promotion, prevention and preparedness (HPPP). Existing and new infectious diseases have gained far more prevalence than expected, and inequities in access to health care accounted for disturbing differences in the toll of these diseases in different populations. The COVID-19 pandemic not only demonstrated the need to prevent the onset and progression of non-communicable chronic diseases (NCDs) and promote healthy lifestyles, but also the need to prepare for new infectious diseases and their long-term effects on both physical and mental health. Preparedness was previously associated with natural disasters, with activities directed to developing emergency humanitarian action response resources. However, these actions are inadequate for the frequent natural disasters as the climate crisis intensifies. To reach effective actions in HPPP, we take a broad approach to HPPP components, identify the main stakeholders and suggest methods to change allocations for HPPP. We propose a call for action at global and national levels, involving strengthening the United Nations' Sustainable Development Goals and government commitment to HPPP.

Measuring intra-individual physical activity variability using consumer-grade activity devices.

Many existing sedentary behavior and physical activity studies focus on primary outcomes that assess change by comparing participants' activity from baseline to post-intervention. With the widespread availability of consumer-grade devices that track activity daily, researchers do not need to rely on those endpoint measurements alone. Using activity trackers, researchers can collect remote data about the process of behavior change and future maintenance of the change by measuring participants' intra-individual physical activity variability. Measuring intra-individual physical activity variability can enable researchers to create tailored and dynamic interventions that account for different physical activity behavior change trajectories, and by that, improve participants' program adherence, enhance intervention design and management, and advance interventions measurements' reliability. We propose an application of intra-individual physical activity variability as a measurement and provide three use cases within interventions. Intra-individual physical activity variability can be used: prior to the intervention period, where relationships between participants' intra-individual physical activity variability and individual characteristics can be used to predict adherence and subsequently tailor interventions; during the intervention period, to assess progress and subsequently boost interventions; and after the intervention, to obtain a reliable representation of the change in primary outcome.

Targeted suppression of human IBD-associated gut microbiota commensals by phage consortia for treatment of intestinal inflammation.

Human gut commensals are increasingly suggested to impact non-communicable diseases, such as inflammatory bowel diseases (IBD), yet their targeted suppression remains a daunting unmet challenge. In four geographically distinct IBD cohorts (n = 537), we identify a clade of Klebsiella pneumoniae (Kp) strains, featuring a unique antibiotics resistance and mobilome signature, to be strongly associated with disease exacerbation and severity. Transfer of clinical IBD-associated Kp strains into colitis-prone, germ-free, and colonized mice enhances intestinal inflammation. Stepwise generation of a lytic five-phage combination, targeting sensitive and resistant IBD-associated Kp clade members through distinct mechanisms, enables effective Kp suppression in colitis-prone mice, driving an attenuated inflammation and disease severity. Proof-of-concept assessment of Kp-targeting phages in an artificial human gut and in healthy volunteers demonstrates gastric acid-dependent phage resilience, safety, and viability in the lower gut. Collectively, we demonstrate the feasibility of orally administered combination phage therapy in avoiding resistance, while effectively inhibiting non-communicable disease-contributing pathobionts.

Backbone metal cyclization: novel 99mTc labeled GnRH analog as potential SPECT molecular imaging agent in cancer.

Gonadotropin-releasing hormone (GnRH) is a decapeptide secreted to the pituitary where it binds to specific receptors on the gonadotropes to regulate gonadotropic hormones (luteinizing hormone (LH) and follicle-stimulating hormone (FSH)) synthesis and secretion. Specific GnRH receptors are overexpressed in breast, prostatic, ovarian, and other tumors. The aim of this study was to synthesize a cyclic GnRH analog with high affinity to GnRH receptors that can be radiolabeled with 99mTc. A precyclic GnRH analog, [Cys-Gly]1[D-Ala]6[N(alpha)(eta-Cys-amino hexyl)]10GnRH (Gn-2), containing two hemi-chelator groups was synthesized. It was cyclized applying the recently reported backbone metal cyclization (BMC) approach, to obtain cyclo(Re(O)1-10)[Cys-Gly]1[D-Ala]6[N(alpha)(eta-Cys-amino hexyl)]10GnRH (cyclo[Re(O)-Gn-2]). For comparative evaluations, Gn-2 was oxidized on-resin to yield cyclo(S-S,1-10)[Cys-Gly]1[D-Ala]6[N(alpha)(eta-Cys-amino hexyl)]10GnRH, (cyclo[S-S-Gn-2]). The binding affinity of cyclo[Re(O)-Gn-2] to rat pituitary membranes showed IC50 of 50 nM, compared to IC50 = 10 nM in the native GnRH. Cyclo(99mTc(O)1-10)[Cys-Gly]1[D-Ala]6[N(alpha)(eta-Cys-amino hexyl)]10GnRH (cyclo[99mTc(O)-Gn-2]) was synthesized from Gn-2 and showed similar chromatographic behavior to its rhenium surrogate.